The current concept of the means by which enzymes exert their catalytic effects requires the intermolecular interactions between the substrate and enzyme to place the substrate(s) and catalyst(s) in the most advantageous position for the reaction to occur. Deviations from this ideal relationship result in a reduced catalytic effect. The objective of this research is to determine the extent to which this concept is true for a class of enzymes - the proteinases. With the determination of the three-dimensional structures of five enzymes in this class, the functional groups with which the substrates interact are known. Using this information the method of monopoles-bond polarizibilities coupled with a hydrogen bonding potential will be employed to calculate theoretically the energy and position of substrate binding to the enzyme active site. The study will deal initially with alpha- chymotrypsin, the most extensively studied enzyme of this group. The theoretically calculated energies and position, when compared with the kinetic data, will reveal: 1) the nature of the D,L specificity; 2) the extent to which the enzyme orients the substrate of the active site; 3) the existence of non-productive modes of binding; 4) the position of the leaving group. By calculating the binding energy of the enzyme-substrate complex in the hypothetical tetrahedral transition state, the ability of the enzyme to induce strain in these substrates can be assessed. In addition, the functional groups predominately responsible for substrate orientation can be determined. This proposal represents the first attempt to quantitate our current concepts of enzymatic catalysis by performing theoretical calculations on actual enzyme-substrate complexes.